Epidemiology of bloodstream infections caused by extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae in Switzerland, 2015-2022: secular trends and association with the COVID-19 pandemic.

BACKGROUND: The association between the COVID-19 pandemic and the incidence of invasive infections caused by multidrug-resistant organisms remains a topic of debate. AIM: To analyse the national incidence rates of bloodstream infections (BSI) caused by Escherichia coli (EC) and Klebsiella pneumoniae (KP) with extended-spectrum cephalosporin resistance (ESCR) in two distinct regions in Switzerland, each exhibiting varying antimicrobial resistance patterns and that were impacted differently by the pandemic. METHODS: Data was analysed from positive blood cultures prospectively collected by the nationwide surveillance system (ANRESIS) from January 1st, 2015, to August 31st, 2022. To explore the potential relationship between COVID-19 patient occupancy and ESCR incidence rates, an in-depth analysis was conducted over the two-year pandemic period from April 1st, 2020, to March 30th, 2022, using Quasi-Poisson and logistic regression analyses. FINDINGS: During the study period, 40,997 EC-BSI and 8537 KP-BSI episodes were collected and reported to ANRESIS by the participating hospitals. ESCR was observed in 11% (N = 4313) of E. coli and 8% (N = 664) of K. pneumoniae, respectively. A significant reduction in ESCR-EC BSI incidence occurred during the pandemic in the region with the highest COVID-19 incidence. Conversely, ESCR-KP BSI incidence initially fell considerably and then increased during the pandemic in both regions, though this effect was not statistically significant. No association between hospital occupancy from COVID-19 patients and these trends was observed. CONCLUSION: In the early phase of the COVID-19 pandemic, a decrease in ESCR rates was observed, particularly in ESCR-EC BSI within the most heavily impacted region.

Impact of intermittent versus continuous infusions on central line-associated bloodstream infection risk in haemato-oncology patients: a quasi-experimental study.

BACKGROUND: Continuous fluid infusions delivered between therapies by piggy-back systems avoid disconnection and reconnection of central venous catheters (CVCs), thereby reducing opportunities for line contamination. However, the impact of continuous versus intermittent infusions on central line-associated bloodstream infections (CLABSIs) is unknown. AIM: To investigate the effect of temporary infusion interruption and line disconnection, with or without use of a 70% isopropyl alcohol cap (IPA-C) on CLABSI rates in haematology patients. METHODS: Quasi-experimental study in two haemato-oncology units. At baseline (P1, September 2020 to August 2021), continuous intravenous piggy-back infusions were mandatory. In a first intervention phase (P2, September 2021 to August 2022), infusion disconnections were implemented with use of a 70% isopropyl alcohol cap (IPA-C) for passive decontamination. In a second intervention phase (P3, September 2022 to August 2023), infusion disconnections continued without the use of IPA-C. Rates of CLABSI were compared across the three intervention periods using segmented Poisson regression. FINDINGS: A total of 11,039 catheter-days across 764 CVCs and 16,226 patient-days were included. Twenty-one CLABSIs were recorded across all intervention periods. Compared with P1, incidence rate ratios (IRRs) for CLABSI did not significantly change in P2 (IRR 0.76 (95% CI 0.27-2.15)) and P3 (IRR 0.79 (95% CI 0.28-2.22)). No CVCs were removed due to occlusion during the study period. Five of 21 CLABSIs were polymicrobial, and coagulase-negative staphylococci were isolated in 19/21 cases (90%). CONCLUSION: Interruption of continuous infusions in haemato-oncology patients with a CVC was not associated with a substantial change in CLABSI rates, whether or not an IPA-C was used.

Risk of catheter-associated bloodstream infection by catheter type in a neonatal intensive care unit: a large cohort study of more than 1100 intravascular catheters.

BACKGROUND: The aim of this study was to evaluate the risk of catheter-associated bloodstream infection (CABSI) among different catheter types using a large prospective database in the neonatal intensive care unit (NICU) of a tertiary care centre in Switzerland. METHODS: We included all neonates admitted to the NICU with at least one central intravascular catheter inserted between January 2017 and December 2020. We used marginal Cox model to determine the risk of CABSI among different catheter types. RESULTS: A total of 574 neonates and 1103 intravascular catheters were included in the study: 581 venous umbilical catheters, 198 arterial umbilical catheters and 324 peripherally inserted central catheters (PICCs). We identified 17, four and four CABSIs in neonates with venous umbilical catheters, arterial umbilical catheters and PICCs, respectively. The risk of CABSI increased after two days of umbilical catheter maintenance. Using univariable Cox models, and adjusting for sex and gestational age, we observed a similar CABSI risk between venous and arterial umbilical catheters (HR 0.57; 95% CI 0.16e2.08). Birth weight was associated with CABSI, with higher weight being protective (HR 0.37, 95% CI 0.16e0.81). CONCLUSIONS: Strategies aimed at reducing umbilical catheter dwell time, particularly in low and very low birth weight neonates, may be effective in decreasing the incidence of CABSI in this population.

Targeted mupirocin-based decolonization for Staphylococcus aureus carriers and the subsequent risk of mupirocin resistance in haemodialysis patients - a longitudinal study over 20 years.

Mupirocin-based decolonization of Staphylococcus aureus carriers undergoing haemodialysis is not widely implemented due to concerns of mupirocin resistance. In our haemodialysis unit, a strategy combining universal S. aureus screening with targeted mupirocin-based decolonization was introduced two decades ago. In this study of haemodialysis patients, mupirocin resistance was assessed in blood and colonizing S. aureus isolates during two periods. Mupirocin resistance in S. aureus was infrequent in both blood and colonizing isolates. Furthermore, in the years 2003-2021, a decreasing trend in the annual rate of S. aureus bloodstream infections was observed. Targeted mupirocin-based decolonization of S. aureus carriers undergoing haemodialysis is a sustainable measure for preventing healthcare-associated infections.

Prevalence and significance of bacterial contamination of autologous stem cell products.

There is limited and conflicting information on the prevalence of contamination of haematopoietic stem and progenitor cell products (HPCPs), and their optimal management remains unclear. The authors reviewed the microbial surveillance data of HPCPs collected between January 2002 and December 2019 for autologous transplantation at the study institution to determine the prevalence of microbial contamination and the potential infectious complications among recipients. Among 3935 HPCPs, 25 (0.6%) were contaminated. Ultimately, 22 patients received contaminated grafts, with pre-emptive antimicrobial therapy initiated in six of these patients. No patients developed subsequent infectious complications. These data suggest that microbial contamination of autologous HPCPs and associated adverse outcomes are rare.

Successful management of a Clostridioides difficile ribotype 027 outbreak with a lean intervention bundle.

BACKGROUND: In a 2015 point-prevalence study, Clostridioides difficile 027, a hypervirulent ribotype, was absent from healthcare institutions in Switzerland. In late 2016, we detected an outbreak of C. difficile infection (CDI) with ribotype 027 occurring across several hospitals in the same hospital network. METHODS: The first cases of CDI due to ribotype 027 triggered an outbreak investigation, including whole genome sequencing (WGS) to identify outbreak strains. FINDINGS: Twenty-eight patients with CDI caused by ribotype 027 between December 2016 and December 2017 were identified, out of which 20 were caused by a single clone. Commonalities among these patients were hospitalization in the same room or on the same ward, receiving care from the same healthcare workers, and shared toilet areas. In addition to the epidemiological links suggesting possible transmission pathways between cases, WGS confirmed the clonality of this C. difficile 027 outbreak. The outbreak was contained by isolation precautions, raising awareness among healthcare workers, harmonizing diagnostic algorithms, and switching to a sporicidal agent for environmental disinfection. Of note, neither default gowning and gloving nor hand washing with water and soap were implemented. CONCLUSION: This C. difficile 027 outbreak was recognized belatedly due to lack of screening for this ribotype in some hospitals, and was contained by a swift response with simple infection prevention measures and adapting the laboratory approach. In order to have a better understanding of C. difficile epidemiology, diagnostic approaches should be standardized, CDI declared notifiable, and longitudinal data on prevalent ribotypes collected in countries where this is not established.

Cefepime neurotoxicity: thresholds and risk factors. A retrospective cohort study.

OBJECTIVES: Toxic serum cefepime trough concentrations are not well defined in the current literature. We aimed to define a more precise plasma trough concentration threshold for this antibiotic's neurological toxicity and to identify individuals at risk for developing neurotoxic side effects. METHODS: Retrospective study including all individuals who underwent cefepime therapeutic drug monitoring (TDM) between 2013 and 2017. Individuals with cefepime concentrations other than trough were excluded. The primary outcome was to assess the incidence of neurotoxicity and its relationship with cefepime plasma trough concentrations. Secondary outcomes were the relationship of renal function, cefepime daily dose, age, and cerebral and general co-morbidities with the occurrence of neurotoxicity. We also compared the mortality rate during hospitalization in individuals with and without neurotoxicity, and the possible impact of neuroprotective co-medications on outcomes. RESULTS: Cefepime concentrations were determined in 584 individuals. Among 319 individuals with available trough concentrations included, the overall incidence of neurotoxicity was 23.2% (74 of 319 individuals). Higher cefepime plasma trough concentrations were significantly associated with risk of neurotoxicity (no neurotoxicity 6.3 mg/L (interquartile range (IQR) 4.1-8.6) versus with neurotoxicity 21.6 mg/L (IQR 17.0-28.6), p <0.001). Individuals with presumed cefepime neurotoxicity had a significantly lower renal function (estimated glomerular filtration rate 82.0 mL/min/1.73 m2 (IQR 45.0-105.0) versus 35.0 mL/min/1.73 m2 (IQR 23.3-53.3], p <0.001), and significantly higher in-hospital mortality (19 (7.8%) versus 26 (35.1%) individuals, p <0.001). No neurotoxic side effects were seen below a trough concentration of 7.7 mg/L. Levels ≥38.1 mg/L always led to neurological side effects. CONCLUSION: In individuals with risk factors for cefepime neurotoxicity, such as renal insufficiency, TDM should be systematically performed, aiming at trough concentrations <7.5 mg/L.

Validity of surrogate endpoints assessing central venous catheter-related infection: evidence from individual- and study-level analyses.

OBJECTIVES: The prevention of catheter-related bloodstream infection (CRBSI) has been an area of intense research, but the heterogeneity of endpoints used to define catheter infection makes the interpretation of randomized controlled trials (RCTs) problematic. The aim of this study was to determine the validity of different endpoints for central venous catheter infections. DATA SOURCES: (a) Individual-catheter data were collected from 9428 catheters from four large RCTs; (b) study-level data from 70 RCTs were identified with a systematic search. Eligible studies were RCTs published between January 1987 and October 2018 investigating various interventions to reduce infections from short-term central venous catheters or short-term dialysis catheters. For each RCT the prevalence rates of CRBSI, quantitative catheter tip colonization, catheter-associated infection (CAI) and central line-associated bloodstream infection (CLABSI) were extracted for each randomized study arm. METHODS: CRBSI was used as the gold-standard endpoint, for which colonization, CAI and CLABSI were evaluated as surrogate endpoints. Surrogate validity was assessed as (1) the individual partial coefficient of determination (individual-pR2) using individual catheter data; (2) the coefficient of determination (study-R2) from mixed-effect models regressing the therapeutic effect size of the surrogates on the effect size of CRBSI, using study-level data. RESULTS: Colonization showed poor agreement with CRBSI at the individual-patient level (pR2 = 0.33 95% CI 0.28-0.38) and poor capture at the study level (R2 = 0.42, 95% CI 0.21-0.58). CAI showed good agreement with CRBSI at the individual-patient level (pR2 = 0.80, 95% CI 0.76-0.83) and moderate capture at the study level (R2 = 0.71, 95% CI 0.51-0.85). CLABSI showed poor agreement with CRBSI at the individual patient level (pR2 = 0.34, 95% CI 0.23-0.46) and poor capture at the study level (R2 = 0.28, 95% CI 0.07-0.76). CONCLUSIONS: CAI is a moderate to good surrogate endpoint for CRBSI. Colonization and CLABSI do not reliably reflect treatment effects on CRBSI and are consequently more suitable for surveillance than for clinical effectiveness research.

Isopropanol at 60% and at 70% are effective against 'isopropanol-tolerant' Enterococcus faecium.

The bactericidal activity of isopropanol was determined against Enterococcus faecium ATCC 6057, ST 796 (isopropanol-tolerant strain) and Enterococcus hirae ATCC 10541 (EN 13727). Isopropanol at 60% and 70% were effective (≥5.38 log10-reduction) in 15 s against all strains but 23% isopropanol was not (<0.99 log10-reduction in ≤15 min). Isopropanol at 70% was tested against E. faecium in the four-field test. Eight millilitres was not effective enough in 1 min (<5 log10-reduction), whilst 16 mL was effective (≥5.85 log10-reduction). Healthcare workers can be reassured that 60% and 70% isopropanol with an appropriate volume are effective against E. faecium.

Low incidence of subsequent bacteraemia or fungaemia after removal of a colonized intravascular catheter tip.

OBJECTIVES: We determined the frequency of subsequent bloodstream infection more than 2 days after removal of a catheter with positive tip cultures. METHODS: We conducted a nationwide, observational study on intravascular catheter (IVC) tip cultures in Switzerland from 2008 to 2015 using data from the Swiss Antibiotic Resistance Surveillance System (ANRESIS). An IVC tip culture was included in the analysis if at least one microorganism could be cultivated from it. We excluded all data from patients with concurrent bacteraemia with the same microorganism identified 7 days before to 2 days after IVC removal. Subsequent bloodstream infection was defined as isolating (from blood cultures performed more than 2 days up to 7 days after catheter removal) the same microorganism as the one recovered from the IVC. Data on antibiotic therapy were not available in this surveillance study. RESULTS: Over the 8-year period, 15 033 positive IVC tip cultures were identified. Our study population comprised 12 513 episodes of positive IVC tip cultures without concurrent bacteraemia. The frequency of sBSI was 1.8% (n = 219). Subsequent bloodstream infections were more frequently detected after identification of C. albicans (10/113, 8.8%), S. marcescens (9/169, 5.3%), and S. aureus (30/623, 4.8%) on a catheter tip. CONCLUSIONS: A very low incidence of subsequent bloodstream infection was observed if a microorganism was identified on a removed IVC tip without concurrent bacteraemia. The risk of subsequent bloodstream infection increased if C. albicans, S. aureus, or S. marcescens were identified in this context.

Patterns and trends of pediatric bloodstream infections: a 7-year surveillance study.

We characterize the epidemiology of pediatric bloodstream infections (BSIs) in Switzerland. We analyzed pathogen distribution and resistance patterns in monomicrobial and polymicrobial BSIs in children from 2008 to 2014 using data from the Swiss antibiotic resistance centre (ANRESIS). A confirmatory statistical analysis was performed comparing pathogens and resistance across 20 acute care hospitals. We identified 3,067 bacteremia episodes, of which 1,823 (59 %) were considered true BSI episodes. Overall, S. aureus (16.5 %, 300) was the most frequent pathogen, followed by E. coli (15.1 %, 276), coagulase-negative staphylococci (CoNS, 12.9 %, 235), S. pneumoniae (11.1 %, 202) and non-E. coli Enterobacteriaceae (8.7 %, 159). S. aureus and E. coli showed similar frequencies in all of the variables analyzed (e.g., hospital acquisition, hospital type, medical specialty). The proportion of these microorganisms did not change over time, resistance rates remained low (4.3 % methicillin resistance in S. aureus; 7.3 % third-/fourth-generation cephalosporin resistance in E. coli), and no significant resistance trends were observed. We observed a 50 % increase of CoNS BSIs from 2008 (9.8 %, 27) to 2014 (15.2 %, 46, p value for trend = 0.03). S. pneumoniae decreased from 17.5 % (48) to 6.6 % (20) during that timeframe (p for trend = 0.007). S. aureus and E. coli remained the most significant pathogens among pediatric BSIs in Switzerland, exhibiting low resistance rates. CoNS accounted for a greater proportion of BSIs over time. The decrease in bacteremic pneumococcal infections can likely be attributed to the introduction of the 13-valent conjugate vaccine in 2011.